Sensor apparatus, systems and methods of making same

ABSTRACT

A sensor system can be configured to perform dielectric spectroscopy (DS). For example, the system can include a sensor configured to measure dielectric permittivity of a fluid in response to an RF input signal. Associated interface electronics can include a transmitter to drive the sensor with the RF input signal and a receiver to receive and process an RF output signal from the sensor in response to the RF input signal.

CROSS REFERENCE TO RELATED APPLICATION

This application is a continuation of application Ser. No. 14/728,642,filed Jun. 2, 2015, and entitled SENSOR APPARATUS, SYSTEMS AND METHODSOF MAKING SAME, which claims the benefit of priority from U.S.Provisional Patent application No. 62/006,560, filed Jun. 2, 2015, andentitled SENSOR APPARATUS, SYSTEM AND METHODS OF MAKING AND USING SAME,each of which is incorporated herein by reference in its entirety.

TECHNICAL FIELD

This disclosure relates to a sensor apparatus, to systems, to methods ofmaking a sensor and to methods of using a sensor for spectroscopy.

BACKGROUND

Quantitative measurement of the complex dielectric permittivity of amaterial versus frequency (e.g., dielectric spectroscopy, also known asDS) can be a powerful monitoring technique with a broad range ofapplications. For example, DS can be utilized for chemical analysis ofoil in the petroleum industry, analysis of substances for security ordefense purposes, soil moisture monitoring in agriculture, fermentationmonitoring during the production of alcoholic beverages, foodquality/safety monitoring and drug development in the pharmaceuticalindustry. DS can also be used as an analytical tool in the biomedicalfield as a label-free, non-destructive and real-time method to study theinteraction of RF/microwave fields with biological/biochemical sampleswith minimal sample preparation. Key molecular characteristics ofbiomaterials such as human blood, spinal fluid, breast tissue and skinhave been studied using DS for applications in disease detection andclinical diagnosis. Typical DS systems tend to be large and expensive,making them cost-prohibitive in certain circumstances.

SUMMARY

This disclosure relates to a sensor system, to methods of making asensor and to methods of using a sensor.

As one example, a sensor includes an input configured to receive aninput radio frequency (RF) signal and an output to provide an output RFsignal. The sensor also includes a capacitive sensor comprisingsubstantially co-planar sensing electrodes, a first of the sensingelectrodes being coupled to the input and a second of the sensingelectrode coupled to the output. The capacitive sensor also including afloating electrode spaced apart from the sensing electrodes by a spacethat defines a fluid channel that is communicatively coupled to receivea fluid material via the fluid port.

As another example, a portable dielectric spectroscopy system mayinclude an integrated sensor interface system comprising a transmitterand a receiver. The transmitter is configured to generate and provide aradio frequency (RF) excitation signal to an output for exciting acapacitive sensor containing a fluid material under test. The receiveris coupled to at least one input to receive an input RF signal and toprovide at least one system signal representing measured transmissioncharacteristics of the capacitive sensor in response to the excitationsignal. A computing system is programmed to calculate a dielectricpermittivity of the material fluid within the channel based on the atleast one system signal.

As another example, a method of fabricating a sensor can include formingsubstantially planar sensor electrodes on a first substrate to provide afirst part of the sensor. An electrically conductive trace extends fromat least one of the sensor electrodes to a termination. The method alsoincludes forming a floating electrode on a wall of a second substrate toprovide a second part of the sensor, a space between the floatingelectrode and the at least one sensor electrode defining a capacitivesensing area within a fluid channel that extends from an openingextending from a surface of the second substrate to the recessed wall.The method also includes attaching the first and second parts of thesensor such that the sensor electrodes are spaced apart from andopposing the floating electrode by a gap to form the fluid channeltherebetween.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts an example of a system to measure dielectricpermittivity.

FIG. 2 depicts an example of a circuit model for a differentialcapacitive sensor of FIGS. 3 and 4.

FIG. 3 depicts an example of a differential dielectric spectroscopysensor.

FIG. 4 depicts a cross sectional view of the sensor of FIG. 3.

FIG. 5 depicts another example of a dielectric spectroscopy sensor.

FIG. 6 depicts a cross sectional view of the sensor of FIG. 5 takenalong line 6-6.

FIG. 7 depicts an example of a circuit model for the capacitive sensorof FIGS. 5 and 6.

FIG. 8 is an assembly view showing part of an example fabricationprocess for making a sensor.

FIG. 9 depicts an example of receiver circuitry that can be implementedin a sensor interface system.

FIG. 10 depicts an example of transmitter circuitry that can beimplemented in a sensor interface system.

FIG. 11 is a graph demonstrating frequency bands that can be provided bythe transmitter circuitry of FIG. 10.

FIG. 12 depicts an example of band select divider circuitry that can beutilized to select frequency bands for exciting a DS sensor.

FIG. 13 depicts an example of frequency divider circuitry that can beutilized in the transmitter circuitry of FIG. 10.

FIG. 14 is a plan view of an example DS microsystem.

FIG. 15 is a flow diagram demonstrating an example method to calibrateand use a DS system.

FIG. 16 is a graph demonstrating permittivity over a range of systemoutputs at a given excitation frequency associated with part of theexample calibration method of FIG. 15.

FIG. 17 is a graph demonstrating a comparison of permittivity over arange of frequencies derived from the DS system disclosed hereinrelative to another system.

FIG. 18 is a graph demonstrating a comparison of complex permittivityover a range of frequencies derived from the integrated DS systemdisclosed herein relative to another system for a given MUT.

FIG. 19 is graph of system outputs in the I mode versus the Q mode suchas can be used to classify a plurality of MUTs.

DETAILED DESCRIPTION

This disclosure relates to a sensor system, to a method of making asensor and to a method of using a sensor. The sensor and associatedinterface electronics can be implemented in a miniaturized platform(e.g., a microsystem) to perform dielectric spectroscopy (DS). Forexample, the sensor can be a microfluidic sensor configured to measuredielectric permittivity of a fluid (e.g., a liquid (e.g., solution) or agas). The associated interface electronics can include a transmitter todrive the sensor with an RF input signal and a receiver to receive an RFoutput signal from the sensor. The interface electronics can beprogrammable to adjust performance and sensitivity of the sensor for awide range of sensing applications. A computing system (e.g., includingmicroprocessor and memory) can be integrated into the DS system forcontrol and data processing to derive DS information, including tocalculate permittivity for a material under test. The derivedinformation and acquired sensor data can be communicated via acommunication link to a remote device, such as for display of the DSinformation.

The DS system can be implemented in a palmtop platform for miniaturizedDS, such as in the MHz-to-GHz range. The DS sensor disclosed herein canbe implemented as microfluidic sensor that includes a three-dimensional,parallel-plate, capacitive structure for extracting complex permittivityof μL-volume materials under test (MUTs). The integrated platform thuscan achieve accurate measurement of real and imaginary parts of complexpermittivity of MUTs with measurement time of a few seconds or faster.As a result, the approach disclosed herein provides rapid,high-throughput, low-cost DS measurements with a self-sustained,low-power, portable instrument.

FIG. 1 depicts an example of a system 10 to measure dielectricpermittivity. The system 10 can include a sensing apparatus 12 and asensor interface system 14. The sensor interface system 14 can drive DSsensor circuitry 16 with an RF input signal (RF_(IN)). The DS sensorcircuitry 16 resides in a fluid channel 18 and is configured to have adielectric permittivity that depends on fluid that is within the fluidchannel 18. For example, a fluid MUT can be provided (e.g., from asource of fluid, such as a micropipette) into the fluid channel 18 viaone or more fluid ports 20. The fluid can be substantially still withinthe channel or it can be flowing through the channel duringmeasurements. The fluid channel can be a microfluidic channel.

As disclosed herein, the DS sensor 16 can include electrodes distributedin the channel 18 in an opposing relationship as to provide a capacitivesensing area between opposing surfaces of the electrodes. For example, afloating electrode can be fixed with respect to a surface of the fluidchannel in a spaced apart opposing relationship from a pair of sensingelectrodes fixed with respect to another surface of the channel. Thepair of sensing electrodes thus can be substantially coplanar along agiven surface of the fluid channel 18 that opposes and is parallel tothe floating electrode. One of the sensing electrodes can be configuredto receive the RF input signal as an excitation signal and the othersensing electrodes can provide a corresponding RF output signal(RF_(OUT)).

The sensor interface system 14 can include a transmitter 22 and areceiver 24. The transmitter 22 can be configured to provide the RFinput signal at a desired excitation frequency. The excitationfrequency, for example, can be in the microwave range. For instance thetransmitter 22 can provide the RF input signal in a range from about 1MHz to about 100 GHz (e.g., from about 5 MHz to about 10 GHz). Theexcitation frequency can be set in response to a program input signal(e.g., by a user input via remote device 30), such as to vary thefrequency according to application requirements. The frequency range forthe excitation signal can be continuous across the range or be providedin two or more discrete frequency bands (see, e.g., FIG. 11), which canbe user programmable.

The receiver 24 is configured to provide an output signal (OUT)representing measured sensor transmission characteristics based on theRF output signal from each DS sensor implemented in the sensingapparatus 12. The output signal can be an analog signal or a digitalsignal. The receiver 24 can include circuitry configured to process theRF output signal, such as by amplifying (e.g., variable gain) andfiltering the RF output signal to ascertain complex signal components ofthe RF output signal, which filtering can be configured according to thefrequency range of the excitation signal. The RF output signal can be acomplex signal corresponding to voltage transmission measurementsthrough the DS sensor 16, which varies as a function of the compleximpedance or admittance as seen at an output node thereof (e.g.,demonstrated at RF_(OUT) in various figures herein). That is, the RFoutput signal can have a predetermined relationship with respect to achange in dielectric permittivity caused by the MUT within the channel18.

The transmitter 22 and receiver 24 can be implemented in an integratedcircuit chip (e.g., system on chip) or they could be implemented asseparate components configured to perform the functions disclosedherein. While the transmitter 22 and receiver 24 are demonstrated inFIG. 1 as co-residing in the interface system 14 (e.g., in a single ICchip), in other examples, the transmitter and receiver could beimplemented as independent separate circuits.

In the example of FIG. 1, the DS apparatus 10 also includes a computingsystem 26. The computing system 26 can be configured (e.g., including aprocessing unit and memory to store instructions and data) to implementDS control 32 to control operating the sensor interface system 14. Forexample, the DS control 32 can selectively control the range offrequencies (e.g., frequency bands) of an RF output signal applied bythe transmitter 22 to each respective DS sensor 16. As mentioned, thetransmitter 22 can provide an excitation signal at one or more discretefrequencies or sweep across one or more predefined frequency bands.

For example, during the first portion of a test phase, DS control 32 cancontrol the transmitter 22 to provide the RF output signal within afirst range of frequencies (e.g., a low frequency range). During asubsequent or other different phase of the sensing process, DS control32 can control the transmitter 22 to provide the RF input signal for adifferent range of frequencies for exciting the DS sensor and theassociated MUT disposed in the fluid channel 18. The receiver 24 thuscan receive and provide corresponding RF output signals associated witheach phase of the sensing process. As disclosed herein, the receiver 24can be configured (e.g., analog and/or digital circuitry) to process thereceived input signal from each DS sensor, such as by performingamplification, filtering and down-conversion. DS control 32 can alsocontrol the receiver to provide the RF output data as a DC outputvoltage in the I mode and another DC output voltage in the Q mode.

The computing system 26 further can include data processing methods forcomputing permittivity in response to the RF output data provided by thereceiver 24 during each part of the sensing process. Thus, the computingsystem 26 further can process the received input signals from a givensensor (or sensors) and provide output data that includes the results ofthe data processing representing complex permittivity as well as rawdata corresponding to the RF output signal received by the receiver.

In some examples, the computing system 26 can also include a calibrationprocess 36 programmed (e.g., see method 500 in FIG. 15) to calibrate thesystem interface system 14 and the DS sensor 16. For example, one ormore reference MUTs (having a known permittivity) can be inserted intothe fluid channel 18 and the DS control 32 can control the transmitter22 to provide the excitation signal (RF_(IN)) to the DS sensor 16 over acorresponding range of frequencies, which can vary according to thereference MUT. For each MUT, the receiver 24 can measure the systemoutput signal (RF_(OUT)) at each respective excitation frequency, whichcan include separate I and Q components. The calibration method 36 canfurther be programmed to fit the measured output signals for eachreference MUT at given frequency to predetermined permittivity valuespredetermined for each respective reference solution. The functionalrelationship between system outputs at each excitation frequency can bestored in memory and utilized by data processing block 32 to convert themeasured system output signal RF_(OUT) at a given excitation frequencyto a corresponding permittivity (e.g., complex permittivity) for anunknown MUT.

As an example, the functional relationship between measured systemoutput signals RF_(OUT) for each of the reference solutions at a givenexcitation frequency can be stored in memory as a look-up tableprogrammed to provide an output of complex permittivity in response tothe measured system output signal RF_(OUT) and input excitation signal.There can be a given LUT for each frequency or the functionalrelationships between permittivity, excitation frequency and measuredoutput can be stored in other forms of data structures or mathematicalfunctions that can computed to calculate complex permittivity for agiven MUT in response to the measured system output signal RF_(OUT) andinput excitation signal. Once the calibration method 36 has beenprogrammed for a set of reference MUTs, the DS apparatus 10 is ready formeasurement and determining complex permittivity for unknown MUTs. It isunderstood that the calibration of the system 10 can be implemented by amanufacturer of the system 10 or prior to conducting measurement by auser in the field.

The computing system 26 can provide the output data to a remote device30 via a corresponding communication system 28. For example, thecommunication system 28 can include a communication interface configuredto communicate data (e.g., via a corresponding communication link),demonstrated at 31. The communication link 31 can be implemented as aphysical connection (e.g., an electrically conductive connection oroptical fiber) or a wireless link (e.g., implemented according an802.11x standard or other short range wireless communication).

The remote device 30 can be communicatively coupled to the DS apparatus10 via the communication link. The remote device 30 can include adisplay 38 that can present the results from the data processing system.This can include graphs or other indications, (including graphics and/ortexts) to provide the user results from the DS applied to the MUT withinthe fluid channel 18. The device 30 can be a general purpose computingdevice (e.g., notebook computer, laptop, desktop computer or the like)or it can be a special purpose device configured to interact with the DSapparatus 10 via the link 31.

The remote device 30 can also include a user interface 40. The userinterface 40 can be utilized to program the DS apparatus 10 for one ormore parts of a sensing process such as disclosed herein. For instance,the user interface 40 can be utilized to set the range of one or morefrequencies, including one or more frequency bands, to be implemented asthe excitation signal during testing of the MUT. For instance, inresponse to user input instructions entered at the remote device via theuser interface 40, the computing system 26 can receive instructions viathe link 31. The computing system 26 can in turn employ its control 32to provide corresponding instructions to program the transmitter 22,which instructions can be stored in memory (e.g., a program register) ofthe transmitter to control the frequency of the excitation signalapplied during a test process. Additionally or alternatively, the userinterface 40 can be utilized to specify one or more MUTs that may haveknown characteristics such as for calibration of the DS apparatus 10.The user interface 40 can also be utilized to control the informationthat is presented in the display 38 as well as other post processingfunctions and data analysis.

In some examples, the sensing apparatus 12 can be configured to includetwo or more of substantially identical sensing structures, eachincluding a respective DS sensor 16 disposed within a respectiveseparate fluid channel 18. For instance, the transmitter can becontrolled to provide excitation signals to each of the different DSsensors 16 having different frequency ranges. For example, if two DSsensors are utilized, the control 32 operates the transmitter 22 toprovides a lower range of frequencies to excite one DS sensor during aportion of the measurement and a higher range of frequencies to excitethe other DS sensor during another, different portion of themeasurement. In this example, each DS sensor could be coupled toseparate front end electronics configured to provide appropriatefiltering and amplification according to the particular frequency rangesapplied to excite each DS sensor. The data processing methods canaggregate the resulting RF output signal from the receiver 24 tocalculate permittivity for each MUT for characterization.

As another example, where one or more pairs of DS sensors are utilized(e.g., example sensor of FIGS. 2-4), the MUT can be provided into thefluid channel 18 of one of the sensing structures and a known material(e.g., having a predetermined dielectric permittivity) can be providedinto the fluid channel of another of the pair of sensing structures. Insuch an example, the sensor interface can provide a differential RFinput signal (e.g., RF+ and RF−) to sensing electrodes of respective DSsensor circuits. Another sensing electrode of each of the DS sensorcircuits can be coupled to a common node to provide the RF output signalto the sensor interface system 14. The RF output signal thus can have apredetermined mathematical relationship with the difference indielectric permittivity for the fluid under test relative to the knownfluid in the other fluid channel. The sensor interface system 14 thuscan be configured to model this relationship and provide an OUTPUTindicative thereof the difference in dielectric permittivity for fluidunder test.

FIG. 2 demonstrates an example of a sensing circuit 50 that could beemployed to model the DS sensor circuitry 16 for the differentialexample disclosed herein. The sensing circuit 50 includes inputs RF+ andRF−, which are driven by differential input voltage +V_(RF) and −V_(RF)having an excitation frequency (ω), such as supplied by transmitter 22.One DS sensor 52 is demonstrated as a capacitor C_(S1) in parallel witha conductance G_(S1). Another DS sensor 54 includes a capacitor C_(S1)in parallel with a conductance G_(S2). The capacitance and conductancescan be related to the excitation frequency ω and the complex dielectricpermittivity of the fluid as follows:

C _(S1) =C ₀(ε′_(r)+Δε′_(r))

G _(S1) =ωC ₀(ε″_(r)+Δε″_(r))

G _(S2) =C ₀ε_(r)′

G _(S2) =ωC ₀ε_(r)″

where the MUT in the channel (e.g., channel 18) has a complex dielectricpermittivity of ε_(r)=ε′_(r)−jε″_(r). Additionally, the capacitivesensing area admittance given the excitation frequency ω, can beexpressed as follows:

Y _(S) =ωC ₀ε_(r) ″+jωC ₀ε′_(r).

The output of the circuit 50 can thus be represented as follows:

V _(OUT) ∝V _(RF) ωC ₀(Δε_(r) ″+jΔε′ _(r))

where the sensor is driven by a differential RF/microwave signal(±V_(RF)) and loaded with a reference solution as well as an SUT with asmall Δε_(r).

FIGS. 3 and 4 depict an example of a three-dimensional sensing DSsensing apparatus 62. The sensing apparatus 62 can be electricallycoupled to a sensor interface system (e.g., interface 14), such as viacontact pins. Other types of connections (e.g., electrically conductiveor wireless) could also be utilized to provide for bi-directionalcommunication with respect to the DS sensing apparatus 62.

In the example of FIGS. 3 and 4, the interface system (e.g., transmitter22) provides differential RF input signals to differential inputs RF+and RF− of the DS sensing apparatus 62. The DS sensing apparatus 62includes circuitry having a complex admittance that varies as a functionof dielectric permittivity of fluid within respective fluid channels,such as disclosed herein. The DS sensing apparatus 62 provides an outputsignal to the interface system via an output connection RF_(OUT) (e.g.,a pin or other type of connection).

In the example of FIGS. 3 and 4, the sensing apparatus 62 includes apair of fluid channels 70 into which a volume of fluid (e.g., liquid orgas) can be introduced via ports 72 (e.g., inlet and outlet holes).Capacitive sensors 74 are disposed within each fluid channel. Eachcapacitive sensor 74 includes a floating electrode 76 spaced apart fromand opposing sensor electrodes 78 and 80 to provide respective sensingareas (e.g., corresponding to the area of overlap between the floatingelectrode and associated sensor electrodes). The sensor electrodes 78and 80 in each capacitive sensor 74 can be electrically isolated fromeach other. The RF+ input signal is coupled to a sensor electrode of oneof the capacitive sensors. The RF− input signal is coupled to a sensorelectrode of another of the capacitive sensors. The other sensorelectrodes of each of the capacitive sensors are coupled to a commonnode electrically coupled to provide RF_(OUT).

As demonstrated in the cross-sectional view of FIG. 4, the each sensor74 includes planar sensor electrodes are separated from a floatingelectrode through a microfluidic channel to form a capacitive sensingarea with nominal air-gap capacitance, C₀, defined by the electrode areaand microfluidic channel height. As mentioned above, at the excitationfrequency, a the capacitive sensing area admittance isY_(S)=ωC₀ε″_(r)+jωC₀ε′_(r), when the channel is loaded with an MUThaving a complex dielectric permittivity of ε_(r)=ε′_(r)−jε″_(r). In theexample of FIGS. 3 and 4, two identical sensing structures 74 are beelectrically connected by a common output node, RF_(OUT), to form adifferential sensor, where V_(OUT)∝V_(RF)ωC₀(Δε″_(r)+jΔε′_(r)) when thesensor is driven by a differential RF/microwave signal (±V_(RF)) andeach separate structure is loaded with a reference solution or an MUTwith a small Δε_(r).

The differential measurement can help enhance the sensing resolution,because the interface IC would not need to measure a very large voltageproportional to the nominal permittivity, ε_(r), as may otherwise be thecase with a single-ended sensor. The exact relationship between V_(OUT)and Δε_(r) depends on the complex impedance (admittance) seen at theoutput node RF_(OUT), which includes the IC input impedance and theparasitic impedance of interconnect. As disclosed herein, the sensor 62and associated parasitic impedances can be modeled, and in-circuitcalibration can be performed employing known reference materials tomodel the relationship between V_(OUT) and Δε_(r) for use in identifyingthe permittivity of the fluid under test and, in turn, characterizingand identifying the fluid. If the parasitic impedance of the contactpins proves to have a significant effect on sensor operation, a reliableelectrical connection through direct wire-bonding of the sensor and ICcan be implemented at the expense of sensor replacement time. Anotherapproach to deal with parasitic impedance is through calibration byincreasing the number of reference solutions at the expense ofcalibration complexity.

As also demonstrated in the cross sectional view of FIG. 4, the sensorcan be fabricated in multiple parts that are attached together toprovide a resultant monolithic sensor structure 62. For example, thesensor 62 can include a top part 84 and a bottom part 86. The bottompart 86 includes sensor electrodes 78 and 80 and RF signal routing(e.g., traces) fabricated on a substrate, which can also include aground plane 88 for the sensor 62. The top part 84 can be fabricatedseparately from the bottom part 86. The top part 84 can include thefluid channel 70 for each sensor structure 74, such as a recess formedin a wall of an insulating substrate material. The top part 84 can alsoinclude inlet/outlet ports 72 to provide fluid communication foraccessing the volume defined by the channel 70. For example, the channel70 and associated ports 72 can be fabricated by micromachining (e.g.,laser micromachining) or by other types of machining or etchingtechniques. In some examples, the surface of channel 70 further can becoated with a polymer or other material (e.g., electrically insulatingfilm, such as poly(ethylene glycol)) to help protect against proteinadsorption onto the surfaces that contact the protein solutions. Thepolymer can be applied via physisorption or chemisorptions, for example.

As one example, the bottom part 86 can be fabricated using standardtechniques with a 4″ borosilicate glass wafer as the substrate. A100-Å/1,000-Å Cr/Au layer can be evaporated on both sides of the wafer.The top metallization can further be patterned with lift-off to createthe sensor electrodes 78 and 80, microstrip signal lines and contactpads. A further bottom metallization can be employed to serve as aground plane for the sensor 62.

As a further example, the microfluidic cap will be fabricated usingpoly(methyl methacrylate) (PMMA). The channel height (e.g., distancebetween top and bottom surfaces of each channel 70) can be establishedaccording to application requirements for the sensor. For instance, achannel height of about 50 μm can be implemented for potential use withhuman blood cells. The floating electrodes can be deposited on the innertop surface of the microfluidic channels by evaporating a 1,000-Å Aulayer and patterning with lift-off.

In the example of FIG. 3, the sensor 62 is demonstrated along with itsterminals that can be electrically connected to interface electronics ona printed-circuit board (PCB). In some examples, the connection betweenthe sensor apparatus 62 and interface system 14 can be configured as aplug-and-play-type connection between the sensor contact pads and PCBinput/output pads (e.g., using spring-loaded contact pins to provide anelectrical connection). The connection method facilitates DSmeasurements with potentially hazardous or contaminating solutions,since the low-cost sensor can be replaced after a measurement withoutcontaminating the entire instrument. That is, in some examples, thesensor 62 can be for single use, which can be discarded and replacedafter each use, while the interface system 64 and associated electronicscan be re-useable. In other examples, the sensor can be repeatedlyreused for a plurality of measurements with the same or different fluidsunder test. The interface system 64 can be calibrated to facilitatemeasuring the dielectric permittivity for a given type of one or morefluids.

As an example, sensor calibration can be performed by loading the sensordifferentially with DI water as a reference solution and a mixture of DIwater and one of several organic solvents (e.g., methanol, isopropylalcohol (IPA)) at various concentrations to produce an SUT with a smallΔε_(r) from that of DI water. The transmission characteristics of thesensor can be measured with a VNA over a range of frequencies (e.g.,from 5 MHz to 10 GHz), and a calibration algorithm can be derived basedon such measurements to relate the complex voltage transmissionmeasurements to Δε_(r). Sensor characterization can be performed insimilar fashion with DI water and a mixture of DI water and ethanol asreference solution and SUT, respectively, and the extracted permittivityfor the mixture will be compared to that from bulk-solution measurementsusing a commercial dielectric probe.

FIGS. 5 and 6 demonstrate an example of another sensing apparatus 100(e.g., corresponding to apparatus 12) that can be utilized in the DSsystem 10. The apparatus 100 includes a three-dimensional,parallel-plate, capacitive sensing structure 102. The capacitive sensingstructure 102 includes two planar sensing electrodes 104 that are spacedapart and are separated from a floating electrode 106 through amicrofluidic channel 108 to form a 3D capacitive sensing area disposedwithin the microfluidic channel. The capacitive sensing structure 102 isdisposed within a substrate material 110. The sensing apparatus 100includes ports 112 (e.g., inlet and outlet holes) through which a volumeof fluid (e.g., liquid or gas) can be introduced.

As also demonstrated in the cross sectional view of FIG. 6, the sensingapparatus 100 can include a top portion 116 and a bottom portion 118(where bottom and top are relative terms simply to provide a frame ofreference in the figure). The bottom portion 116 can include sensorelectrodes 104. The electrodes can be electrically connected viaelectrically conductive sidewalls of respective vias 120. Theelectrically conductive vias thus can provide a path for RF signalrouting between the respective electrodes 104 and associated electricalcontact pads 122 fabricated on the substrate 118. In some examples, thetop part 116 may be fabricated separately from the bottom part 86. Thetop part 116 can include the fluid channel 108 between ports 112 andextending between the floating electrode 106 and the sensing electrodes104.

In some examples, a thin film or other surface coating (e.g., having athickness that is smaller than the microfluidic channel height) can beapplied to prevent direct contact between the MUT and the metalelectrodes with minimal impact on sensitivity. As the MUT passes throughthe capacitive sensing area, the impedance (and hence admittance) of thesensor changes based on the dielectric permittivity of the MUT disposedin the channel 108.

FIG. 7 depicts an example of a circuit model 130 for the sensor of FIGS.5 and 6. The circuit 130 model includes two series connected capacitors132 (e.g., capacitors formed between floating electrode 106 and sensingelectrodes 104 of FIGS. 5 and 6).

By way of example, at the measurement frequency, ω, the admittance ofthe capacitive sensing area can be expressed as follows:

Y _(S) =jωC ₀(ε_(r) ′−jε″ _(r))

which further can be represented by its real and imaginary parts ofsensor admittance as follows:

${{{Imag}\left( \frac{Y_{s}}{\omega} \right)} = {{C_{0} \times ɛ_{r}^{\prime}\mspace{14mu} {and}\mspace{14mu} {{Real}\left( \frac{Y_{s}}{\omega} \right)}} = {C_{0} \times ɛ_{r}^{''}}}},$

where C₀ is the nominal, series-connected, air-gap capacitance of theparallel-plate, capacitive sensing area, and ε′_(r) and ε″_(r) are thereal and imaginary parts of the complex relative permittivity of theMUT, respectively.

In practice, parasitic inductance and parasitic capacitance from thevias 120 and contact pads 122 can be accounted for by implementing acalibration method, such as disclosed herein (see, e.g., calibrationmethod 500 of FIG. 15).

Applying the sensing apparatus 100 in the context of the DS system 10,an input RF signal (e.g., sweeping over one or more frequency ranges)can be applied (e.g., by transmitter 22) to an input electrode 122 forexciting the sensing circuit. A resulting RF output signal can bemeasured at the other sensing electrode 122 (e.g., by receiver 24). Themeasured signal can be filtered and amplified (e.g., by analog and/ordigital circuitry of receiver 24) and processed (e.g., by dataprocessing 34 of computing system 26) to calculate permittivity for theMUT that resides within the channel 108. As disclosed herein, the dataprocessing can be implemented to accurately measure both real andimaginary parts of the complex relative permittivity over a broad rangeof frequencies.

FIG. 8 illustrates an example of the sensor fabrication and assemblythat can be employed to produce the sensing apparatus 100 of FIGS. 5 and6. As an example, the sensing apparatus 100 can be constructed aslaminated device that includes three layers, namely a connector layer150, a channel layer 152 and a fluidic layer 154. The connector layer150 can be fabricated from a substrate material (e.g., commerciallyavailable, 0.5 mm-thick, Rogers 4350 PCB). Sensing electrodes 104 can beformed (e.g., using the top PCB metal layer) on the adjacent surface ofthe connector layer. As one example, the electrodes 104 may beimplemented to have dimensions of about 0.6 mm×0.6 mm with spacing of0.4 mm. Electrical connections to the sensing electrodes 104 are madethrough vias in the substrate (e.g., PCB) of the connector layer 150,which can be electrically connected to the sensor interface system(e.g., to transmitter 22 and receiver 24 of interface 14) by connectorsattached to the pads on the bottom side of the substrate layer 150 (notshown).

The channel layer 152 includes the microfluidic channel 108 formedtherein. For instance, the channel can be laser-cut into anon-conductive material layer that is interposed between the layers 150and 154. The layer 152 can be a thin film layer of double-sided-adhesive(DSA) material having a thickness that is much less than theelectrode-containing layers 150 and 154. As one example, the layer 152is about 250 μm thick, whereas the layer 150 is about 0.5 mm thick andlayer 154 is about 3.2 mm thick. Other relative thicknesses can beutilized according to application requirements.

The fluidic layer 154 can be formed from a layer an electricallynon-conductive material, such as a layer of an acrylic (e.g., PMMAacrylic) material. For instance, the fluid ports 112 can be formed(e.g., by laser micromachining) through the side surfaces of the caplayer as to overly spaced apart end portions of the channel 108. Thefloating electrode 106 can be formed by deposition of electricallyconductive material deposited at a desired location (e.g., aligned withthe sensing electrodes and within the channel 108) on the bottom surfacethat faces the surface of the layer 150 where the sensing electrodes areformed. For instance, the floating electrode 106 can be an electricallyconductive material (e.g., gold, copper or aluminum) deposited on theinner top surface of the cap by sputter deposition using a shadow maskand lift-off process. As an example, the floating electrode can beformed with a thickness of 1000 angstroms and dimensions of 1.2 mm×2.8mm aligned with sensing electrodes having dimensions of 0.6 mm×0.6 mm,each.

To facilitate construction of the sensing apparatus 100, each of thelayers 150, 152 and 154 can include a plurality of alignment holes 156.Each of the layers can be connected together and held in place byinserting corresponding alignment pins 158 can be inserted into theholes 156. In some examples, a thin film coating of a barrier material(e.g., 1.5 μm layer of Parylene-N film or other polymer film) can bedeposited on the surfaces of the layers 150 and 154 to protect the metaland plastic surfaces from direct contact with the MUT.

Microfluidic inlet/outlet holes 112 in the cap layer can be configuredwith a diameter to fit a standard micropipette tip. As one example, themicrofluidic channel has a total sample volume of 9 μL and a volume of0.8 μL in the sensing area under the floating electrode. Other volumesfor the channel and sensing area can be implemented according toapplication requirements. The sensor 100 can be assembled by attachingthe cap to the surface of the PCB substrate using the DSA filminterposed therebetween. As mentioned, the alignment holes 156 and pins158 can be used to align the microfluidic channel and floating electrodeover the sensing electrodes.

FIG. 9 depicts an example of a receiver circuit 200, which can beimplemented as receiver 24 in FIG. 1. The receiver circuit 200 isconfigured to measure transmission characteristics of the DS sensor(e.g., sensor 16) in voltage domain based on an output V_(OUT) from thesensor. While in the example of FIG. 9, the receiver 200 provides ananalog output at system outputs (System_(—OUT)+ and System_(—OUT)−), insome examples, the receiver can include an analog-to-digital converter(ADC) to provide a digital output for further processing correspondingto System_(—OUT)+ and System_(—OUT)−. Additionally, the design of the RX200 can include an optimized architecture to extend the operationfrequency to 10 GHz or greater.

The receiver 200 includes one or more inputs 202 and 204 to receiveinput signals from the sensor responsive to signals provided by atransmitter (e.g., transmitter 22) to excite the sensor, as disclosedherein. In some examples, a single input 202 or 204 may suffice formeasuring transmission characteristics. In other examples, such as wherea more broadband range of frequencies are applied to the sensor, morethan one input 202-204 can be used.

In the example of FIG. 9, the receiver 200 includes a pair of inputs 202and 204, demonstrated respectively at HF_RFin and LF_RFin, where eachinput is used for measuring a different range of frequencies. Thus, eachinput 202 and 204 is connected to drive associated front end circuitsconfigured to perform front-end processing (e.g., filtering,amplification and mixing) for a predefined range of frequencies (e.g.,about 200 MHz to about 5 GHz). For instance, the input HF_RFin isprovided at 202 to a high bandwidth (HBW) path that includes a HBWlow-noise amplifier 206. The HBW LNA 206 can perform single todifferential conversion and provide an amplified differential output toan HBW mixer 208. The mixer 208 (e.g, a Gilbert-cell active mixer) candown convert the amplified signals from the amplifier 206 based on localoscillator input signals LO+ and LO− to provide IF signals (e.g.,concerting input frequency in the range of MHz to GHz down to IF ofabout 1 MHz). The signals LO+ and LO− can be provided by transmittercircuitry (see FIG. 10). The IF differential signals can be provided toa multiplexer 210.

Similarly, the input LF_RFin is provided at 204 to a low bandwidth (LBW)path that includes a LBW LNA 212. The LBW LNA 212 is configured toperform single to differential conversion and provide an amplifieddifferential output to an LBW mixer 214 based on frequency downconversion according to local oscillator input signals LO+ and LO. Thefrequency-converted, LBW differential signals can be provided to themultiplexer 210. The multiplexer can be operated to pass either thepre-processed HBW or LBW signals to a high-pass filter 216 depending onthe frequency range of the excitation signals, which can be set asprogrammable control signals (e.g., from control 32 of computing system26).

By way of example, an external bit (or other control input, such asprovided by control 32) can be set to control a multiplexer 210 to routethe appropriate front end module output to the input of a coherentdetector for a second down-conversion step. Since, in someimplementations, each of the front end RF modules will have independentpower supplies, they can be turned on and off independently. Thisfeature allows the user to save power by using the LBW RF module only,in case the experiment does not require GHz-range excitationfrequencies, for example. Additional controls can be provided to setbias currents for the different front end modules.

The receiver 200 further can implement amplification of the IF signalfrom the filter with gain and temperature calibration. For example, thehighpass filter 216 can provide a filtered output signal to differentialinputs of an intermediate frequency (IF) variable gain amplifier stage218 that is configured to provide temperature compensation. Atemperature sensor 220 can be activated in response to a trigger inputat 222 to provide a temperature compensated gain value to a multiplexer224. For example, the gain of the first VGA can be adjusted by a digitaloutput of the on-chip temperature sensor 220 to compensate for gaindecrease versus temperature in a defined temperature range (e.g., 0 to60° C.).

The multiplexer 224 can switch between the temperature signal andanother gain calibration input to calibrate the IF VGA 218. The IF VGA218 can provide the temperature compensated amplified IF output toanother IF VGA 226 for additional amplification according to a gaincalibration (Gain_Cal2), which can be fixed or variable. The IF VGA 226provides its amplified output to a passive mixer 230. Each of IF VGAscan be operated in response to bias control currents supplied to thereceiver 200.

The amplified/filtered IF signal can be down-converted to DC via apassive mixer 230 and low pass filter 240. For example, a clock drives adigital I/Q generator with a clock signal (e.g., 1-MHz) and thenphase-adjusted using a phase calibration module (PCM). The PCM canprovide square-wave, I/Q signals to the passive mixer 230. Given thepath delay experienced by sensor response signal at each excitationfrequency, the fine PCM 234 can refine delay to I/Q signals (same delayto preserve the 90° phase shift) before they drive the passive mixer230. The I/Q signals output of the passive mixer 230 can be low passfiltered and provide the output signal System_(—OUT)+ andSystem_(—OUT)−. For instance, output signal System_(—OUT)+ andSystem_(—OUT)− can be provided to an ADC for generating a correspondingdigital output signal for further processing (e.g., by data processingmethods 34).

The LNAs 206 and 212 and, mixers 208 and 214 thus provide a broadbandlock-in architecture, to down-convert the sensor response signal at theRF/microwave excitation frequency to an IF frequency. The next stagesand passive mixing provide additional down-conversion to dc using acoherent detector to extract the dc component of the system output. Thedc component would be proportional to the imaginary (real) part ofsensor V_(OUT) in I(Q) mode of system operation. While the example ofFIG. 9 shows two different bandwidth paths, fewer or greater numbers ofpaths could be utilized in other examples to accommodate differentfrequency ranges.

FIG. 10 depicts and example of a transmitter circuit 300 such ascorresponding to the transmitter 22 of FIG. 1. The transmitter 300 isconfigured to generate differential RF excitation signals, demonstratedas RF_OUT+ and RF_OUT−, for exciting a sensor (e.g., sensor 16)connected at outputs 302 and 304. The transmitter 300 can also generatelocal oscillation signals (LO+ and LO−) for use in down-convertingsignals by the receiver circuitry 200. As an example, the operationfrequency can range from about 1 MHz to about 10 GHz, such as can becontrolled in response to control inputs from an associated computingsystem (e.g., control 32 of computing system 26). For example,transmitter 300 can provide the excitation signal in a range defined byone of a plurality of predefined frequency bands. For example, thetransmitter 300 can be set to one or more desired pre-selected specificfrequency points in response to a band select signal (e.g., set inresponse to control signal from control 32). Alternatively, thefrequency synthesizer can be configured to sweep the excitationfrequency over one or more specific ranges in response to the bandselect signal (e.g., set in response to control signal from control 32).

By way of further example, the transmitter 300 includes an integer-Nfrequency synthesizer 306 operating in a predefined range (e.g., fromabout 1 MHz to about 10 GHz) to provide the RF output signal at 302 and304. The frequency synthesizer 306, for example, includes aphase-frequency detector (PFD) 308, current-programmable charge pump310, loop filter 312, quadrature VCO (QVCO) 314. The QVCO can includeboth coarse and fine tuning. The frequency synthesizer 306 can alsoinclude a buffer 316 that provides a buffered output to an input of aband select multiplexer 318 as well as to a divider (e.g., a ÷2 divider)320. The output of divider 320 can drive a programmable frequencydivider 322 with a ratio (N) in a predetermined range according to thevalue of the programmable input (e.g., ranging from 150 to 320). Theoutput of divider 320 can also provide another frequency band input tothe multiplexer 318 as well as drive band select dividers 324. The bandselect dividers 324 can include an arrangement of band-select, frequencydivide-by-2 blocks (see, e.g., FIG. 12) configured to generate lowerexcitation frequencies (e.g., from about 1 MHz to about 5 GHz. Theoutput of the multiplexer 318 is selected based on a band select controlsignal to provide local oscillator signal (e.g., a differential signalLO+ and LO−) to a clock buffer 326. The multiplexer 318 thus can routethe generated differential LO signal to both the RX circuitry (receiver200) and a clock buffer 326.

The transmitter 300 further can include a mixer 328 configured togenerate the excitation signal for the sensor 106 by mixing the LO+ andLO− signal (from clock buffer 326) with a predetermined low frequencysignal (e.g., 1-MHz signal). For example, the input clock signal (e.g.,a 16-MHz reference clock) can be provided to a frequency divider 332(e.g., a divide-by-16 divider) and filtered by low-pass filter 330 toprovide a filtered RF signal at a desired frequency that is supplied tothe mixer 328. The mixer 328, for example, is a harmonic-rejection,single-sideband (HR-SSB) mixer, which can reject the up-converted aswell as 3^(rd)/5^(th) harmonic mixing terms at its output, resulting ina nearly single-tone excitation signal at 302 and 304 for the sensor.Further, the mixer 328 can inherently have a differential output toallow driving a differential sensor, if desired. Additionally, the mixercan employ a programmable conversion gain for tunability in theexcitation amplitude (±V_(RF)) to ensure that V_(OUT) can lie within theinput dynamic range of the IC for a desired range of Δε_(r).

As a further example, the synthesizer 306 can be configured to have aconstant loop gain K (∝K_(VCO)×I_(cp)/N), such as by keeping a constantVCO gain factor (K_(VCO)) and varying the charge pump current (I_(cp))in proportion to the programmable frequency-divide ratio (N). This canhelp ensure stability and constant settling time for the synthesizerwithin the entire frequency range of operation.

FIG. 11 is a graph 350 demonstrating a plurality of frequency bands thatcan be provided by the transmitter 300 of FIG. 10. In the example ofFIG. 11, eight discrete bands in a continuous range from 9.75 MHz to2.432 GHz are depicted. Each band can be generated to provide respectiveI and Q components for each band.

As a further example, FIG. 12 depicts an example the band select dividercircuitry 324 that can provide each of the bands, such as the bandsshown in FIG. 10. The band select divider circuitry 324 can include anarrangement of band-select, frequency divide-by-2 blocks 360 configuredto supply respective differential frequency outputs of two for each ofthe I and Q components. The differential I and Q outputs are provided tobuffers for each band. Each buffer 362 supplies its differential signalat a prescribed frequency to inputs of the multiplexer 318, whichselects a respective band, including its I and Q components, based onthe band select input.

FIG. 13 depicts band divider 360 that can be implemented in the bandselect divider circuitry 324 to divide the generated frequency signalinto respective frequency bands for use within the transmitter circuitryof FIG. 10. In the example of FIG. 13, the band divider 360 isdemonstrated as divide-by-two circuit of a pair of D-flip flopsconnected in series; although other approaches (e.g., analog or digitalcircuitry) can be used to implement frequency dividers for therespective bands. One of the flip-flops provides the differential Qcomponents for a respective frequency band and the other flip-flopprovides the differential I components for the respective frequencyband. Any number of such band dividers can be connected together toaccommodate any number of bands with a desired frequency range.

As a further example, FIG. 14 depicts another example of a DSmicrosystem that can be implemented as an integrated palmtop system,such as within the design specifications of Table 1. Table 1 provides anexample of some target performance metrics that can be implemented for aDS microsystem (e.g., the system 10 or 400; as well as the systemcomprising circuits 200, 300 and sensor 16. The components of the sensorcan be constructed of biocompatible materials, such as including gold,glass and PMMA, commonly used in biomicrofluidic devices.

TABLE 1 SUMMARY OF EXAMPLE TARGET PERFORMANCE Sensor - Size: 15 × 15 × 2mm³; Sample Volume: ~1 μL/channel Interface IC - Size: 4 × 4 mm² (in 90nm RF CMOS); Supply: 1.2 V; Power: <100 mW DS Microsystem - Freq: 5MHz-10 GHz; Δε_(r,max) = 1-100 (programmable by V_(RF)); Δε_(r,min) =0.001 (Δε_(r,max) = 1)

In the following description of FIG. 14, components of the system 400are referred to using similar reference numbers refer to componentspreviously introduced with respect to FIG. 1. The system 400 can includea sensing apparatus 12 and associated interface electronics 14. In theexample of FIG. 14, the sensing apparatus 12 includes multiple DSsensors 16 (e.g., corresponding to the example sensor structure 100 ofFIGS. 5 and 6). Thus, the sensor 16 and interface electronics 14 can beconfigured to produce a complex output that depends on (e.g., varies asa mathematical function of) the complex permittivity of fluid disposedin a microfluidic sensor channel of each DS sensor 16.

For example, a micropipette (or other device) 402 can be employed toinject a MUT into the microfluidic channel of each sensor 16. In thisexample, assume that the same MUT is injected into each channel. Inother examples, a reference material and an MUT can be injected intochannels of different sensors. The sensor interface electronics 14includes transmitter circuitry 22 to provide an excitation signal (e.g.,at single frequency or a range of one or more bands) to an input of agiven sensor containing a volume of the MUT. The transmitter canprovider another different excitation signal can be provided to theother DS sensor over a frequency range (e.g., one or more bands). Theoutputs of each sensor 16 are coupled to respective front-end RF modules404 (demonstrated at FE_1 through FE_N, where N is a positive integerdenoting the number of front end modules, which can be the same as thenumber of sensors) of the receiver (e.g., receiver 24). Each front-endRF module 404 is configured to preprocess (e.g., performdown-conversion, filtering and amplification) each transmitted signalreceived in response to an excitation signal and provide correspondingIF signals, such as disclosed with respect to FIG. 9. The IF signalsfrom a given one of the front-end RF module 404 can be selectivelyprovided to other receiver circuitry 406 for further processing into asystem output signal (e.g., differential signal system_out+ andsystem_out−).

The system output signal can be converted to a digital version of thesignal and provided to computing module 26. The computing module 26 cancalculate permittivity for the MUT based on the system output signal toprovide corresponding output data. The output data can include complexpermittivity values (e.g., real and imaginary permittivity) computedover the aggregate range of excitation frequencies, including differentsubranges provided to each DS sensor 16. Output data can also includeraw signal measurements and the input excitation frequencies. Thecomputing module 26 can further provide the output data to acommunication module 28. The communication module 28 can send the outputdata and raw measurement data to an external device. For example, thecommunication module 28 can wirelessly transmit the output data to anexternal device (e.g., a smartphone or tablet computer) for further dataprocessing and/or to display the information to the user. The externaldevice can also wirelessly transmit command information to themeasurement system 400 to program one or more of the system parameters(e.g., signal gain and/or frequency range) to control its operation. TheDS microsystem 400 of FIG. 14 can include a housing that contains thesensor interface electronics 14, computing module 26 and communicationmodule 28 such that it can provide a portable, palm top structure.

The computing module 26 can also implement a calibration method (e.g.,calibration method 36 or 500) that functionally relates the measured RFoutput of the dielectric spectroscopy microsystem 400 to the complexpermittivity of the MUT in the sensor channel over a range of excitationfrequencies. By way of example, FIG. 15 is a flow diagram demonstratingan example method (e.g., corresponding to calibration method 36 ofFIG. 1) 500 implemented by an integrated computing system to calibratethe DS system 400. An in-circuit calibration procedure mitigates theeffects of parasitic circuit elements and enables the data processingmethods (e.g, data processing 34 of FIG. 1) to accurately characterizethe admittance of the capacitive sensing area, Ys. The calibrationmethod 500 can be an automated or semi-automated process in response toa user input. The calibration method 500 can be based on a linear ornonlinear fit of the sensor output characteristics loaded with referencecalibration materials, each having a known complex permittivity at aknown temperature and over a range of excitation frequencies. Forexample, the process can be performed at room temperature (or otherknown temperature) immediately prior to the measurement of the MUT tominimize the effects of ambient variations. In other examples, thiscalibration process can be performed at a plurality of differenttemperatures to determine the calibration coefficients over an ambienttemperature range.

At 502 permittivity values for a set of reference solutions can bestored in memory. For example, the permittivity values can be measuredfor a set of reference solutions to characterize complex dielectricpermittivity (e.g., ε′_(r,ref) and ε″_(r,ref)) for each referencesolution over a range of test frequencies. In some examples, themeasurements can be part of the method 500. In other examples, thecomplex permittivity of a set of reference solutions can be determined apriori apart from the method 500. As an example, the measurementsimplemented to determine the permittivity values at 502 can be obtainedusing a commercially available DS device (e.g., Agilent 85070EDielectric Probe Kit or the like) over a frequency range set accordingto the capabilities of the network analyzer. The range of frequencies,for example, encompass the expected range of excitation frequencies tobe applied (e.g., by transmitter 22) to excite the MUT in the DS sensordisclosed herein. As a further example, the sensor system is calibratedusing a plurality of six reference materials (e.g., air, isopropylalcohol (IPA), methanol, 1:3 IPA:methanol, 1:1 IPA:methanol and 3:1IPA:methanol). Of course, other reference solutions can be used.

At 504, a given one of the reference solutions for which permittivitywas determined at 502 is loaded into the DS sensor, and the systemoutput of the sensor is measured (e.g., by receiver 24) over a range ofexcitation frequencies (e.g., provided by transmitter 22). For example,the range of excitation frequencies can be the same or at least overlapwith the frequency range used to characterize the complex permittivityof the reference solutions (at 502). As a further example, themeasurements at 504 for a given reference solution can be obtained as aset of output voltages over a range of frequencies by operating thetransmitter 22 in the I mode. Then, another set of measurements can beobtained as another set of output voltages over the range of frequenciesby operating the transmitter 22 in the Q mode. As disclosed herein,system outputs measured by receiver 24 during the I mode is functionallyrelated to the real part of dielectric permittivity (e.g.,V_(OUT.I)˜ε′_(r,ref)) and the system output measured during the Q modeis functionally related to the imaginary part of dielectric permittivity(e.g., V_(OUT.Q)˜ε″_(r,ref)) for each respective excitation frequency.

At 506, a determination is made whether there are any additionalreference solutions. If additional solutions exist (YES), the methodproceeds from 506 to 508 to repeat the measurements at 504 for the nextsolution over a corresponding range of excitation frequencies (e.g.,applied by the transmitter 22 based on controls 32 of computing system26). There can be any number of one or more reference solutions. Oncethere are no more reference solutions, the method can proceed from 506to 510.

At 510, the measured system outputs (e.g., for each of the I mode and Qmode) are fit to the real and imaginary permittivity data over a setexcitation frequencies. For example, the receiver can (e.g., in responseto controls 32) convert the measured output signals from the DS sensorto corresponding DC receiver outputs for each of the I and Q modes ofsystem operation (see, e.g., receiver 200 of FIG. 9). As an example, thecalibration method employs a 1^(st)-order polynomial fit to relate thereal and imaginary parts of dielectric permittivity (e.g., ε′_(r,ref)and ε′_(r,ref)) information to I- and Q-mode measurement valuesV_(OUT.I) and V_(OUT.Q) results, respectively, corresponding to systemoutputs from the receiver. For example, the fitting at 510 can producecoefficients that define a linear mathematical relationship between eachof the real and imaginary parts of dielectric permittivity and the DCsystem output voltages measured for each reference solution at a givenfrequency. The relationships between complex permittivity and systemoutputs (e.g., linear coefficients) can be determined from the fittingat 510 for each of the excitation frequencies. The fitting at 510 can beperformed for each excitation frequency, for example, by computing alinear least-squares fit between the known real permittivity ε′_(r,ref)of the reference calibration materials (from 502) and the V_(OUT.I)measured by the sensor at 504 during the I mode. Similarly, the fittingat 510 for each excitation frequency can also compute a linearleast-squares fit between the known ε″_(r,ref) of the referencecalibration materials (from 502) and the V_(OUT.Q) measured by thesensor at 504 during the Q mode. Examples of fitting outputs to real andimaginary permittivity for an excitation frequency of 1 GHz are shown inFIG. 16. Similar linear functions can be determined for other excitationfrequencies.

The resulting coefficients computed for each of a plurality offrequencies can be stored in memory to calibrate the permittivitycalculator (e.g., data processing method 34), at 512. The permittivitycalibration at 512 can include storing an indication of the determined(e.g., linear or non-linear) relationship between permittivity andsystem I and Q system outputs. For example, one or more look-up tablesare programmed to provide an output of complex permittivity in responseto the measured system output signal RF_(OUT) for an input excitationsignal at a given frequency for each of the I mode and Q mode. In otherexamples, the functional relationships to calibrate the permittivitycalculation at 512 can be stored in other forms of data structures ormathematical functions (e.g., linear function or non-linear function)that can computed to calculate complex permittivity for a given MUT inresponse to the measured system output signal RF_(OUT) and inputexcitation signal.

Based on the calibration at 512, the calibrated data processing methodscan then be employed (e.g., by the data processing methods 34), at 514,to ascertain permittivity (complex relative permittivity, ε′_(r,ref) andε″_(r,ref)) in response to system output signals generated by receiverin response to one or more excitation signals provided to one or more DSsensor containing an MUT within the fluid channel thereof. For example,controls can operate the transmitter to provide the excitation signalfor a range of one or more excitation frequencies to interrogate the MUTin the DS sensor. The receiver can be controlled (e.g., in response tocontrols 32) to provide respective system DC voltage outputs for each ofthe I mode and Q mode (V_(OUT.I) and V_(OUT.Q)). In response to theV_(OUT.I) and V_(OUT.Q), which can be converted to digital values (e.g.,by an ADC integrated in the interface electronics or external to theinterface), the real and imaginary permittivity values can be computedfor each frequency that is applied to the DS sensor, and the resultingreal and imaginary permittivity values determined can be aggregated toprovide a corresponding calculated complex permittivity for the MUT (at514), such as shown in the examples of FIGS. 17 and 18.

FIG. 16 is a graph demonstrating plots 520 and 530 representing complexpermittivity as a function DC system output for an excitation signalapplied (e.g., by transmitter 22) as part of the calibration method ofFIG. 15. In the example of FIG. 16, plots 520 and 530 show therelationship between sensor output data and permittivity for sixreference materials for an excitation signal applied at 1 GHz in each ofthe I mode and the Q mode. In the example, of FIG. 16, the referencesolutions used for sensor calibration consist of phosphate-bufferedsaline (PBS) plus a small amount of alcohol (10% ethanol, 5% ethanol,2.5% ethanol, 10% methanol, 5% methanol, and 2.5% methanol). The plot520 depicts a relationship between real permittivity of a plurality ofreference solutions measured by the dielectric probe kit and DS sensoroutput measurements (e.g., provided by receiver 24). The othercalibration plot 530 relates imaginary permittivity of the referencesolutions measured by the dielectric probe kit to DS sensormeasurements. In both plots 520 and 530, the dashed line shows a linearfit to the data. As mentioned, fit parameters (e.g., coefficients) canbe determined for each measurement frequency and stored in memory andapplied for computing complex permittivity for a given MUTs (e.g, at 514of FIG. 15). Once the calibration coefficients are determined and usedto calibrate the permittivity calculator (e.g, at 512 of FIG. 15), thepermittivity calculation (at 514 of FIG. 15) can be used for any otherPBS-based MUT to extract the complex permittivity information from thecorresponding voltage measurements.

FIG. 17 includes a graph of plots 550 and 560 demonstrating complexpermittivity over a range of frequencies for a PBS reference solution.In particular, plot 550 demonstrates a comparison of real permittivityderived from a calibrated DS microsystem (e.g., 10 or 400), which isimplemented according to the approach disclosed herein, compared topermittivity measurements from a standard system (e.g., a dielectricprobe kit and a variable network analyzer (VNA)). Similarly, plot 560shows a comparison of imaginary permittivity derived from a calibratedDS microsystem (e.g., 10 or 400) and permittivity measurements from thestandard network analysis system. Thus, from FIG. 17, it is shown thatthe DS microsystem and related data processing methods disclosed hereinenable accurate determination of complex permittivity over a broad rangeof frequencies.

FIG. 18 depicts a graph of plots 570 and 580 demonstrating real andimaginary parts of complex relative dielectric permittivity vs.frequency for an MUT implemented as vodka (e.g., Smirnoff, 80 proof)measured by a DS system (e.g., system 10 or 400) at 32 RF excitationfrequencies ranging from 10 MHz to 2.4 GHz. In this example, it isassumed that a 6-point calibration was performed with referencesolutions of DI water and DI water with a small amount of alcohol (5%ethanol, 10% ethanol, 5% IPA, 10% IPA, and 20% IPA). Solid line depictsthe measured curve with a standard probe (e.g., Agilent 85070Edielectric probe) interfaced with a VNA as a bulk-solution referencemeasurement from a typical benchtop setup.

FIG. 19 is a graph (e.g., a classification diagram) that includes plots600, 610, 620 and 630 of measured DC system outputs in the I mode versusDC system outputs in the Q mode over four different frequencies for aplurality of different MUTs. Graphs of the type shown in FIG. 19 can begenerated by the DS system (e.g., system 10 or 400) and displayed (e.g.,on device 30) to characterize a plurality of MUTs in the absence ofcalibration. Thus, while permittivity is not computed for each sample,the relationship between DC system outputs in each of the I and Q modesaffords a relative classification among the MUTs for each differentexcitation frequency. In the example of FIG. 19, plot 600 shows themeasured DC system output in I/Q modes at about 50 MHz, plot 610 showsthe measured DC system output in I/Q modes at about 500 MHz, plot 620shows the measured DC system output in I/Q modes at about 1.5 GHz andplot 630 shows the measured DC system output in I/Q modes at about 2.4GHz. The measured outputs demonstrated in FIG. 19 show the respectivemeasured DC system outputs in I/Q modes with the sensor loaded withMUTs, including DI water, phosphate-buffered saline (PBS), MILLER LITE®beer and GUINNESS® beer, as four examples of primarily-water-based MUTs.Since the dielectric relaxation characteristics of free water moleculeswould dominate the response at sufficiently high excitation frequencies,the MUT responses were much closer to each other at 2.4 GHz compared to50 MHz, as evident by the much smaller dynamic range of X-Y axis.Nonetheless, a palmtop version of the DS system disclosed is fullycapable of differentiating among the four MUTs across a range offrequencies.

In view of the foregoing, the DS microsystem disclosed herein thus canprovide a low-power, low-cost and portable instrument for rapidlyextracting key information that characterizes the molecular structure ofbiological solutions in a broad frequency range using p L-samplevolumes, thereby paving the way for a more widespread use of DS inscientific research and clinical settings. The proposed differentialmeasurement technique at the sensor level can be utilized to achievehigh resolution in permittivity measurements by simultaneously comparingtwo similar solutions such as an unmodified protein solution and onethat has undergone a structural change. The approach disclosed hereincan also mitigate the effect of temperature-induced permittivityvariation, because the temperature difference between the two biologicalsolutions in close physical proximity would be very small. Further,planar electrodes have been widely implemented in the past due to thereduced fabrication requirements of routing all signals on a singlelayer. However, electric (E)-field variation near the surface of aplanar electrode requires the MUT to be in direct contact with the metalelectrode, because a surface coating would greatly reduce thesensitivity. The constant E-field in a parallel-plate, capacitivesensing area can solve such E-field variation.

As disclosed herein, the example parallel-plate, capacitive sensor basedon a novel 3D-gap with floating electrodes (see, e.g., FIGS. 3-7) can beimplemented to simultaneously achieve the advantages of a constantE-field and the reduced fabrication requirements of a single layer forsignal routing. Additionally, the interface electronics (e.g., interface14), as disclosed herein, can be implemented on a single-chip CMOS ICthat integrates both sensor excitation and read-out functions forautonomous operation over a frequency range spanning >3 orders ofmagnitude from MHz to GHz. Further, separating the fabrication of thesensor and IC allows for sensor replacement, facilitating DS studies onpotentially contaminating solutions without affecting the entireinstrument.

What have been described above are examples. It is, of course, notpossible to describe every conceivable combination of structures,components, or methods, but one of ordinary skill in the art willrecognize that many further combinations and permutations are possible.Accordingly, the invention is intended to embrace all such alterations,modifications, and variations that fall within the scope of thisapplication, including the appended claims.

Where the disclosure or claims recite “a,” “an,” “a first,” or “another”element, or the equivalent thereof, it should be interpreted to includeone or more than one such element, neither requiring nor excluding twoor more such elements. As used herein, the term “includes” meansincludes but not limited to, and the term “including” means includingbut not limited to. The term “based on” means based at least in part on.

What is claimed is:
 1. A system, comprising: an integrated sensor devicecomprising: a transmitter configured to generate and provide a radiofrequency (RF) excitation signal that varies over a range of excitationfrequencies to an output for exciting a capacitive sensor containing avolume of biological fluid material under test; and a receiver coupledto at least one input to receive an input RF signal and to provide atleast one system signal representing measured transmissioncharacteristics of the capacitive sensor, which varies as a function ofdielectric permittivity of the biological fluid material under test inresponse to the RF excitation signal over the range of excitationfrequencies; wherein an estimate of the dielectric permittivity of thebiological fluid material under test is derived based on the measuredtransmission characteristics of the capacitive sensor.
 2. The system ofclaim 1, wherein the biological fluid material under test comprisesblood cells.
 3. The system of claim 1, wherein the integrated sensordevice further comprises a communication module configured tocommunicate data, including the measured transmission characteristics ofthe capacitive sensor, via a communications link.
 4. The system of claim3, further comprising a remote device communicatively coupled to theintegrated sensor device via the communications link.
 5. The system ofclaim 4, wherein the communication module is configured to transmit rawmeasurement data to the remote device, and wherein the remote device isconfigured to process the raw measurement data.
 6. The system of claim4, wherein the remote device further comprises a display to presentinformation to a user based on the estimate of the dielectricpermittivity of the biological fluid material under test.
 7. The systemof claim 4, wherein the remote device is one of a smart phone, a tabletcomputer, notebook computer, laptop or desktop computer.
 8. The systemof claim 4, wherein the communications link is wireless.
 9. The systemof claim 1, wherein the integrated sensor device includes a computingsystem configured to compute the estimate of the dielectric permittivityof the biological fluid material under test based on the measuredtransmission characteristics of the capacitive sensor.
 10. The system ofclaim 1, wherein the capacitive sensor of the integrated sensor devicecomprises electrodes spaced apart from each other to define a fluidchannel that is configured to receive the volume of biological fluidmaterial under test.
 11. The system of claim 10, wherein the integratedsensor device further comprises a fluid input port adapted to receivebiological fluid material under test and provide the volume ofbiological fluid material under test to the fluid channel.
 12. Thesystem of claim 10, wherein the electrodes of the capacitive sensorfurther comprise: substantially co-planar sensing electrodes, a first ofthe sensing electrodes being coupled to the input and a second of thesensing electrodes coupled to the output; and a floating electrodespaced apart from the sensing electrodes by a space that defines thefluid channel that is communicatively coupled to receive a fluidmaterial under test via at least one fluid port.
 13. The system of claim1, wherein the estimate of the dielectric permittivity includes complexpermittivity over the range of excitation frequencies.
 14. A methodcomprising: introducing a volume of a biological fluid material undertest through an inlet port and into a space between spaced apart platesof a capacitive sensor of an integrated sensor device; providing a radiofrequency (RF) excitation signal that varies over a range of excitationfrequencies to an output such that the capacitive sensor containing thevolume of biological fluid material under test is excited; and receivingan input RF signal from the capacitive sensor and providing at least onesystem signal representing measured transmission characteristics of thecapacitive sensor, which varies as a function of dielectric permittivityof the biological fluid material under test in response to the RFexcitation signal over the range of excitation frequencies; and derivingan estimate of the dielectric permittivity of the biological fluidmaterial under test based on the measured transmission characteristicsof the capacitive sensor.
 15. The method of claim 14, wherein thebiological fluid material under test comprises blood cells.
 16. Themethod of claim 14, further comprising: communicating data from theintegrated sensor device to a remote device via a communications link,the data including at least one of raw measurement data or the estimateof the dielectric permittivity.
 17. The method of claim 16, furthercomprising: processing, at the remote device, the data communicated fromthe integrated sensor device; and displaying, at the remote device,information based on the processing of the data.
 18. The method of claim16, wherein the communications link is wireless, and wherein the remotedevice is one of a smart phone, a tablet computer, notebook computer,laptop or desktop computer.
 19. The method of claim 14, wherein thecapacitive sensor of the integrated sensor device comprises electrodesspaced apart from each other to define a fluid channel that is adaptedto receive the volume of biological fluid material under test.
 20. Themethod of claim 14, wherein the estimate of the dielectric permittivityincludes complex permittivity over the range of excitation frequencies.